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Enhancement of NK Cell Antitumor Effector Functions Using a Bispecific Single Domain Antibody Targeting CD16 and the Epidermal Growth Factor Receptor. | LitMetric

AI Article Synopsis

  • Natural Killer (NK) cells are promising for cancer therapy because they can kill tumor cells while keeping safety in check.
  • A new bispecific single domain antibody (VHH) targets both NK cells and tumor cells, activating NK cells to effectively destroy tumors regardless of KRAS mutations.
  • The study found that this VHH increased the cancer cell-killing ability of NK cells from colorectal cancer patients, suggesting it may be useful for future therapies alone or in combination with other treatments.

Article Abstract

The ability to kill tumor cells while maintaining an acceptable safety profile makes Natural Killer (NK) cells promising assets for cancer therapy. Strategies to enhance the preferential accumulation and activation of NK cells in the tumor microenvironment can be expected to increase the efficacy of NK cell-based therapies. In this study, we show binding of a novel bispecific single domain antibody (VHH) to both CD16 (FcRγIII) on NK cells and the epidermal growth factor receptor (EGFR) on tumor cells of epithelial origin. The bispecific VHH triggered CD16- and EGFR-dependent activation of NK cells and subsequent lysis of tumor cells, regardless of the KRAS mutational status of the tumor. Enhancement of NK cell activation by the bispecific VHH was also observed when NK cells of colorectal cancer (CRC) patients were co-cultured with EGFR expressing tumor cells. Finally, higher levels of cytotoxicity were found against patient-derived metastatic CRC cells in the presence of the bispecific VHH and autologous peripheral blood mononuclear cells or allogeneic CD16 expressing NK cells. The anticancer activity of CD16-EGFR bispecific VHHs reported here merits further exploration to assess its potential therapeutic activity either alone or in combination with adoptive NK cell-based therapeutic approaches.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582566PMC
http://dx.doi.org/10.3390/cancers13215446DOI Listing

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